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      The Synergistic Toxicity of Pesticide Mixtures: Implications for Risk Assessment and the Conservation of Endangered Pacific Salmon

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          Abstract

          Background

          Mixtures of organophosphate and carbamate pesticides are commonly detected in freshwater habitats that support threatened and endangered species of Pacific salmon ( Oncorhynchus sp.). These pesticides inhibit the activity of acetylcholinesterase (AChE) and thus have potential to interfere with behaviors that may be essential for salmon survival. Although the effects of individual anticholin-esterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood.

          Objectives

          We assessed whether chemicals in a mixture act in isolation (resulting in additive AChE inhibition) or whether components interact to produce either antagonistic or synergistic toxicity.

          Methods

          We measured brain AChE inhibition in juvenile coho salmon ( Oncorhynchus kisutch) exposed to sublethal concentrations of the organophosphates diazinon, malathion, and chlorpyrifos, as well as the carbamates carbaryl and carbofuran. Concentrations of individual chemicals were normalized to their respective median effective concentrations (EC 50) and collectively fit to a nonlinear regression. We used this curve to determine whether toxicologic responses to binary mixtures were additive, antagonistic, or synergistic.

          Results

          We observed addition and synergism, with a greater degree of synergism at higher exposure concentrations. Several combinations of organophosphates were lethal at concentrations that were sublethal in single-chemical trials.

          Conclusion

          Single-chemical risk assessments are likely to underestimate the impacts of these insecticides on salmon in river systems where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in salmon habitats may pose a more important challenge for species recovery than previously anticipated.

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          Most cited references66

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          Application and validation of approaches for the predictive hazard assessment of realistic pesticide mixtures.

          In freshwater systems located in agricultural areas, organisms are exposed to a multitude of toxicologically and structurally different pesticides. For regulatory purposes it is of major importance whether the combined hazard of these substances can be predictively assessed from the single substance toxicity. For artificially designed multi-component mixtures, it has been shown that the mixture toxicity can be predicted by concentration addition (CA) in case of similarly acting substances and by independent action (IA), if mixtures are composed of dissimilarly acting substances. This study aimed to analyse whether these concepts may also be used to predictively assess the toxicity of environmentally realistic mixtures. For this purpose a mixture of 25 pesticides, which reflects a realistic exposure scenario in field run-off water, was studied for its effects on the reproduction of the freshwater alga Scenedesmus vacuolatus. The toxicity of the tested mixtures showed a good predictability by CA. This is consistent with the finding that the toxicity was dominated by a group of similarly acting photosystem II inhibitors, although the mixture included substances with diverse and partly unknown mechanisms of action. IA slightly underestimated the actual mixture toxicity. However, the EC(50) values that can be derived from each prediction, according to CA respectively IA, only differed by a factor of 1.3. The finding of such a small difference is partly explainable by the fact that only few components dominate the mixture scenario in terms of so-called toxic units (TUs). This connection is established by developing an equation that allows to calculate the maximum possible ratio between corresponding predictions of effect concentrations by IA and CA for any given ratio of the TUs of mixture components, irrespective of their individual concentration-response functions and independent from their mechanisms of action. To evaluate whether small quantitative differences between EC(50) values predicted by CA and IA are an exception or rather the rule for agricultural exposure scenarios, this calculation was applied on an additional set of 18 pesticide exposure scenarios that were taken from the literature. For these scenarios, EC(50) values predicted by IA can never exceed those predicted by CA by more than a factor of 2.5. The findings of this study support the view that CA provides a precautious but not overprotective approach to the predictive hazard assessment of pesticide mixtures under realistic exposure scenarios, irrespective of the similarity or dissimilarity of their mechanisms of action.
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            Pesticides in the Diets of Infants and Children

            (1993)
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              • Abstract: not found
              • Article: not found

              Pesticides in U.S. streams and groundwater.

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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                March 2009
                14 November 2008
                : 117
                : 3
                : 348-353
                Affiliations
                [1 ] NOAA (National Oceanic and Atmospheric Administration) Fisheries, Northwest Fisheries Science Center, Seattle, Washington, USA
                [2 ] Food and Environmental Quality Laboratory, Washington State University, Richland, Washington, USA
                [3 ] Department of Entomology, Ecotoxicology Program, Washington State University, Puyallup, Washington, USA
                Author notes
                Address correspondence to N.L. Scholz, NOAA Fisheries, Northwest Fisheries Science Center, 2725 Montlake Blvd. E., Seattle, WA 98112 USA. Telephone: (206) 860-3454. Fax: (206) 860-3335. E-mail: nathaniel.scholz@ 123456noaa.gov

                The authors declare they have no competing financial interests.

                Article
                ehp-117-348
                10.1289/ehp.0800096
                2661902
                19337507
                80e24112-dd75-4f74-816e-7637e725835a
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 14 August 2008
                : 13 November 2008
                Categories
                Research

                Public health
                carbamates,acetylcholinesterase,salmon,conservation,organophosphates,synergy,pesticides,risk assessment,toxicity

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